Essential Elements for a GMP Analytical Chemistry Department

202 Pages·2013·4.29 MB·English

by  Thomas Catalano (auth.)

Thomas Catalano
Essential Elements
for a GMP Analytical
Chemistry
Department
Essential Elements for a GMP Analytical
Chemistry Department
Thomas Catalano
Essential Elements
for a GMP Analytical
Chemistry Department
123
ThomasCatalano Ph.D.
PharmChem Analytical ConsultantsLLC
Buffalo Grove, IL
USA
ISBN 978-1-4614-7641-2 ISBN 978-1-4614-7642-9 (eBook)
DOI 10.1007/978-1-4614-7642-9
SpringerNewYorkHeidelbergDordrechtLondon
LibraryofCongressControlNumber:2013938176
(cid:2)SpringerScience+BusinessMediaNewYork2013
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This Book is dedicated to my Wife Jeanie
Who helped with the Manuscript
And is A Lifelong Friend
Preface
Thisvolumepresentsasystematicapproachtounderstandingtheessentialelements
required for a successful GMP analytical chemistry department to function as an
efficient and effective organization. It describes in detail a department structure
which allows for the necessary processes tobecome available toall its personnel.
This department structure facilitates the free flow of information and interactions
within the department. The environment and culture created by this approach
encouragesandrewardsthesharingofideas,skills,andabilitiesamongdepartment
personnel.
The essential elements such as SOPs, regulatory guidances/guidelines, project
teams,technicalanddepartmentprocesses,statisticalconcepts,outsourcing,men-
toringandhiringthebestareamongthemanytopicsthatarediscussedindetailand
how they can be implemented to build an efficient and effective analytical
department.
EssentialEelementsforaGMPAnalyticalChemistryDepartmentcanbeanasset
to all companies that perform GMP analytical method development, validation,
analyses,etc.Thisbookisanessentialadditiontothelibraryforallstart-ups,generic
pharmaceuticalcompanies,andcontractresearchorganizations.Inaddition,itcan
beanimportantsubjectaspartofauniversityPharmaceuticalTechnologyprogram.
Thomas Catalano, Ph.D.
Buffalo Grove, IL
USA
vii
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
2 Organization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.1 Department Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2.2 Project Teams . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
2.2.1 Project Team Development and Management . . . . . . . 5
2.2.2 Risk Evaluation. . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2.2.3 Project Team Dynamics . . . . . . . . . . . . . . . . . . . . . . 8
2.3 Responsibilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
2.4 Interactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
2.5 Operating Guidance’s. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2.5.1 SOP’s and Guidelines. . . . . . . . . . . . . . . . . . . . . . . . 16
2.5.2 Regulatory Guidance’s . . . . . . . . . . . . . . . . . . . . . . . 17
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
3 Processes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.1 Safety Process. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.2 Technology Processes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
3.2.1 Systematic Approach to HPLC Method
Development. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
3.2.2 Dissolution Method Development . . . . . . . . . . . . . . . 39
3.2.3 Systematic Approach to Method Validation. . . . . . . . . 43
3.2.4 Analytical Technology Transfer Process. . . . . . . . . . . 53
3.3 Departmental Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
3.3.1 Specification Development Process . . . . . . . . . . . . . . 56
3.3.2 Stability Management Process. . . . . . . . . . . . . . . . . . 87
3.3.3 Reference Standard Certification Process . . . . . . . . . . 95
3.3.4 Training . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
ix
x Contents
4 Statistical Concepts for the Analytical Chemist. . . . . . . . . . . . . . . 111
4.1 Distribution. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
4.1.1 Student’s t Distribution. . . . . . . . . . . . . . . . . . . . . . . 112
4.1.2 Chi-Squared Distribution ðx2Þ . . . . . . . . . . . . . . . . . . 113
4.1.3 The F Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . 113
4.2 Significance Testing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
4.2.1 Arithmetic Mean . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
4.2.2 Median. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
4.2.3 Standard Deviation. . . . . . . . . . . . . . . . . . . . . . . . . . 114
4.2.4 Standard Error of the Mean. . . . . . . . . . . . . . . . . . . . 114
4.2.5 Relative Standard Deviation
(Coefficient of Variation) . . . . . . . . . . . . . . . . . . . . . 115
4.2.6 Hypotheses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
4.2.7 Significant Testing. . . . . . . . . . . . . . . . . . . . . . . . . . 115
4.3 Confidence Intervals for the Mean. . . . . . . . . . . . . . . . . . . . . 117
4.4 Outliers in Analytical Data . . . . . . . . . . . . . . . . . . . . . . . . . . 118
4.5 Regression Analysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
4.6 Design of Experiments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
4.7 Required Sample Replicates . . . . . . . . . . . . . . . . . . . . . . . . . 124
4.8 Method Performance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
4.8.1 Method Precision. . . . . . . . . . . . . . . . . . . . . . . . . . . 126
4.8.2 Accuracy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
4.8.3 Linearity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
4.8.4 Limit of Detection (LOD). . . . . . . . . . . . . . . . . . . . . 128
4.8.5 Limit of Quantitation (LOQ). . . . . . . . . . . . . . . . . . . 129
4.8.6 Ruggedness. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
4.9 Measurement Uncertainty . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
4.10 Sampling Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
4.10.1 Simple Random Sampling. . . . . . . . . . . . . . . . . . . . . 134
4.10.2 Stratified Random Sampling . . . . . . . . . . . . . . . . . . . 135
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
5 Outsourcing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
5.1 Process. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
5.2 Audit Form (Check List). . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
6 Documentation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
6.1 Sample Submission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
6.2 Technical Reports . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
6.2.1 Development Reports. . . . . . . . . . . . . . . . . . . . . . . . 153
6.2.2 Method Validation Report. . . . . . . . . . . . . . . . . . . . . 153
6.2.3 Analytical Development Report. . . . . . . . . . . . . . . . . 153
6.2.4 Stability Report . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
Contents xi
6.3 Analysis Report. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
6.4 Records . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
7 Job Descriptions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
7.1 Career Tracks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
8 Motivating Personnel. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
8.1 Career Path. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
9 Hiring the Best . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
9.1 Hiring the Best . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
Reference. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
Appendix I: Project Plan Development Checklist . . . . . . . . . . . . . . . . 181
Appendix II: Project Strategy Document . . . . . . . . . . . . . . . . . . . . . . 183
Appendix III: Project Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . 187
About the Author . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
Abbreviations
%R Percent risk change between plans
c
%R Percent total risk of current plan
t
%R Percent risk evaluation of determined low risk plan
XL
ACN Acetonitrile
AD Analytical Department
AL Analytical Lead
API Active Pharmaceutical Ingredient
BA Bioavailability
BCS Biological classification system
BE Bioequivalence
CDA Confidentiality agreement
CFR Code offederal regulations
CI Confidence interval
CMC Chemistry manufacturing and controls
CoA Certificate of analysis
CTD Common technical document
CTM Clinical trial material
DAD Diode array detector
DC Development compound
Deg. Prds Degradation products
Disc Discovery
DMPK Drug metabolism pharmacokinetics
DOE Design of experiments
DSC Differential scanning calorimetry
EC Electron capture detector
FID Flame ionization detector
GC Gas chromatography
GLP Good laboratory practices
GMP Good manufacturing practices
HLA Highest level of authority
HPLC High performance liquid chromatography
ICH International conference on harmonization
ID Identity, identification
xiii